Thought disorder and nucleus accumbens in childhood: a structural MRI study.
ABSTRACT Thought disorder has been described as a hallmark feature in both adult and childhood-onset schizophrenia. The nucleus accumbens (NAc) has been repeatedly proposed as a critical station for modulating gating of information flow and processing of information within the thalamocortical circuitry. The aim of the present study was to investigate the relationship of thought disorder measures, which were administered to 12 children with schizophrenia and 15 healthy age-matched controls, and NAc volumes obtained from high-resolution volumetric magnetic resonance imaging analyses. The propensity for specific thought disorder features was significantly related to NAc volumes, despite no statistically significant differences in the NAc volumes of children with schizophrenia and normal children. Smaller left NAc volumes were significantly related to poor on-line revision of linguistic errors in word choice, syntax and reference. On the other hand, underuse of on-line repair of errors in planning and organizing thinking was significantly associated with decreased right NAc volumes. The results of this pilot study suggest that the NAc is implicated in specific thought patterns of childhood. They also suggest that subcortical function in the NAc might reflect hemispheric specialization patterns with left lateralization for revision of linguistic errors and right lateralization for repair strategies involved in the organization of thinking.
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ABSTRACT: To evaluate changes in functional connectivity as a result of treatment with antipsychotic drugs (APDs) in subjects with schizophrenia (SZ), we identified a limited number of regions that have been implicated in the mechanism of action of APDs and that are part of a neuronal network known to be modulated by dopamine (DA). These regions consisted of the nucleus accumbens (NAcc), the hippocampus (Hip), and the medial frontal cortex (MFC). SZ participants were blindly randomized into a haloperidol treatment group (n = 12) and an olanzapine treatment group (n = 17). Using PET with 15O, we evaluated changes in functional connectivity between these regions during rest and task performance at three treatment time points: (1) at baseline, after withdrawal of all psychotropic medication (2 weeks), (2) after 1 week on medication, and (3) after 6 weeks on medication. Results from the two treatment groups were combined during analysis to investigate the common effects of APDs on functional connectivity. We found that the functional connectivity between MFC and NAcc significantly increased at week one, and then significantly decreased from week one to week 6. The functional connectivity between MFC and Hip significantly decreased at week one and week 6 relative to baseline. Critically, the strength of the functional connectivity between the MFC and Hip after 1 week of treatment was predictive of treatment response. This pattern of changes may represent an important biomarker for indexing treatment response. The regulation by APDs of the balance between prefrontal and limbic inputs to the striatum may be crucial to restoring adaptive behavior.Frontiers in Psychiatry 12/2012; 3:105. DOI:10.3389/fpsyt.2012.00105
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ABSTRACT: Animal studies have found that the phasic activity of dopamine neurons during reward-related learning resembles a "prediction error" (PE) signal derived from a class of computational models called reinforcement learning (RL). An apparently similar signal can be measured using fMRI in the human striatum, a primary dopaminergic target. However, the fMRI signal does not measure dopamine per se, and therefore further evidence is needed to determine if these signals are related to each other. Parkinson's disease (PD) involves the neurodegeneration of the dopamine system and is accompanied by deficits in reward-related decision-making tasks. In the current study we used a computational RL model to assess striatal error signals in PD patients performing an RL task during fMRI scanning. Results show that error signals were preserved in ventral striatum of PD patients, but impaired in dorsolateral striatum, relative to healthy controls, a pattern reflecting the known selective anatomical degeneration of dopamine nuclei in PD. These findings support the notion that PE signals measured in the human striatum by the BOLD signal may reflect phasic DA activity. These results also provide evidence for a deficiency in PE signaling in the dorsolateral striatum of PD patients that may offer an explanation for their deficits observed in other reward learning tasks.NeuroImage 09/2009; 49(1):772-81. DOI:10.1016/j.neuroimage.2009.08.011 · 6.13 Impact Factor
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ABSTRACT: Although structural changes of the basal ganglia are widely implicated in schizophrenia, prior findings in chronically medicated patients show that these changes relate to particular antipsychotic treatments. In unmedicated schizophrenia, local alterations in morphological parameters and their relationships with clinical measures remain unknown. Novel surface-based anatomical modelling methods were applied to magnetic resonance imaging data to examine regional changes in the shape and volume of the caudate, the putamen and the nucleus accumbens in 21 patients (19 males/2 females; mean age=30.7+/-7.3) who were either antipsychotic-naïve or antipsychotic-free for at least 1 year and 21 healthy comparison subjects (19 males/2 females; mean age=31.1+/-8.2). Clinical relationships of striatal morphology were based on exploratory analyses. Left and right global putamen volumes were significantly smaller in patients than controls; no significant global volume effects were observed for the caudate and the nucleus accumbens. However, surface deformation mapping results showed localized volume changes prominent bilaterally in medial/lateral anterior regions of the caudate, as well as in anterior and midposterior regions of the putamen, pronounced on the medial surface. A significant positive correlation was observed between right anterior putamen surface contractions and affective flattening, a core negative symptom of schizophrenia. The diagnostic effects of local surface deformations mostly pronounced in the associative striatum, as well as the correlation between anterior putamen morphology and affective flattening in unmedicated schizophrenia suggest disease-specific neuroanatomical abnormalities and distinct cortical-striatal dysconnectivity patterns relevant to altered executive control, motor planning, along with abnormalities of emotional processing.Schizophrenia Research 10/2008; 106(2-3):140-7. DOI:10.1016/j.schres.2008.08.025 · 4.43 Impact Factor